Re-Imagining Surface Plasmon Resonance for Characterizing Biomolecular Interactions

Using the latest technologies to reinvent existing tools makes these platforms more accessible to a broader range of laboratories

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Surface plasmon resonance (SPR) is a powerful technique for observing biomolecular interactions due to its ability to quantitatively measure real-time interactions without the need for labels or markers. While SPR and the related technology Bio-Layer Interferometry (BLI) are critical tools in the discovery and development of biologics, the widespread adoption of conventional systems is often hindered by prohibitive upfront and maintenance costs, a steep learning curve, and high sample consumption.

“Nicoya’s mission is to improve human life by helping scientists succeed,” emphasized Ryan Denomme, CEO and founder of Nicoya Lifesciences. “To provide a more accessible, cost-effective and efficient solution for the use of SPR in biologics discovery and development, we built Alto™ —a next-generation digital SPR instrument.”

Using Technology to Remove Barriers

The innovative SPR method, called digital SPR™, bypasses existing barriers. dSPR integrates digital microfluidics (DMF) with robust localized SPR (LSPR). DMF is an advanced technology at the intersection of microfluidics and electronics. It leverages an array of individually controlled electrodes to manipulate droplets like discrete bits of data, enabling the execution of programmed protocols on precise quantities of liquid on a micro- and nanoscale.

Nicoya Alto x Model
Nicoya Alto Digital SPR System

Launched in 2020, Alto is reportedly the only SPR platform to integrate DMF with nanotechnology-based biosensors. This solution miniaturizes and automates assays. Designed to be user friendly and accessible, Alto takes the complexity out of SPR while providing high-quality analytical data. This next-generation plug-and-play SPR platform streamlines research workflows, standardizes experimental protocols and eliminates user-to-user variation, while significantly minimizing sample and time requirements. Furthermore, Alto is automation compatible.

Coupling nanotechnology-based biosensors directly onto a DMF-based disposable cartridge eliminates the need for pumps and valves that are found in traditional SPR systems. In addition, the fluidics-free Alto uniquely offers the ability to analyze complex samples that would otherwise pose a challenge with conventional SPR systems.

All the end user needs to do is pipette the samples and reagents into the disposable cartridge, place it in the instrument, choose a preconfigured protocol in the platform’s intuitive cloud-connected software, and start the experiment. Everything happens inside the cartridge. While traditional technologies like BLI require copious amounts of samples, the miniaturized nanotech-based analysis in Alto only requires a sample volume of 2 µL.

“Alto streamlines workflows to provide high-quality affinity, kinetics, quantitation, and epitope characterization data, while reducing the cost and time of discovery,” said Denomme.  “The economical footprint and cost, combined with 16-channel throughput, makes SPR available to a wider base of laboratories to use in an expanded set of applications.”

Expanding Applications

Biomolecular interactions promote the regulation and execution of most biological processes in the body and, thus, are often at the heart of therapeutic discovery. Early drug discovery relies heavily on the characterization of these interactions to validate new targets and observe their binding to new drugs.

SPR, a gold standard tool for streamlining the hit discovery and confirmation phase, provides a molecule-agnostic, reproducible approach for binding affinity and kinetics analysis. The platform generates comprehensive data on multiple interaction characteristics in parallel, including affinity, kinetics, concentration, and specificity, minimizing experimentation time.

Alto further enhances studies by automating all sample manipulation and data analysis and unlocking crude sample compatibility, often a limitation of fluidics-based SPR systems. Screening of compounds in complex media broadens its application in initial discovery and determination of compound interaction with serum proteins, which has important implications for early ADME/PK and bioavailability assessment.

A recent application note demonstrated Alto’s capability in virology and vaccine development. The digital SPR instrument was used to successfully screen for H5N1 Influenza A hemagglutinin using a capture screening feature to quickly test and select best candidates.

The high-throughput digital SPR Alto fits a wide range of applications for characterizing biomolecular interactions, including in-depth kinetics and affinity characterization, screening, quantitation, and epitope mapping and binning. Researchers can leverage Alto to characterize a wide range of targets, including oligonucleotides, Fcγ receptors, mAbs, biosimilars, bispecifics, virus-like particles, lipid nanoparticles, and viral targets.

 

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